Performance and survival outcomes of defect-driven versus specimen-driven method of frozen section intraoperative margin assessment in oral cancers.

Margin status is one of the most important prognostic factors in oral cancers. Intraoperative frozen section (FS) can be performed to ensure a margin-negative resection, however the method of FS assessment is debatable. The aim of this study was to compare the defect-driven (DDA) versus specimen-driven (SDA) approach for intraoperative assessment of tumour margins in oral cancer resections and their impact on loco-regional recurrence and survival. The primary study endpoint was margin status determined from the final histopathological examination report. Secondary endpoints were disease recurrence and survival. This retrospective cohort study compared the two methods of FS in terms of their performance and survival outcomes. All oral squamous cell carcinoma patients who underwent surgery as the primary treatment from January 2018 to February 2019 were included. The involved margin rate was slightly lower with SDA than DDA (7.5% vs 11.8%), however the difference was not statistically significant. The recurrence rate was higher with DDA (19/51, 37.2%) than SDA (14/53, 26.4%), although this was not statistically significant. Local recurrence-free survival (DDA 62% vs SDA 75%; P = 0.653) and overall survival (DDA 76% vs SDA 78%; P = 0.300) at 18 months of follow-up were comparable. There was no significant difference in sensitivity or specificity of intraoperative FS for margin assessment between SDA and DDA. The type of intraoperative FS technique used did not affect loco-regional recurrence or overall survival.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Socioeconomic factors in timing of esophagectomy and association with outcomes.

BACKGROUND AND OBJECTIVES: Disparities in esophageal cancer are well-established. The standard treatment for locally advanced esophageal cancer is chemoradiation followed by surgery. We sought to evaluate the association between socioeconomic factors, time to surgery, and patient outcomes. METHODS: All patients ≥18 years old diagnosed with T2/3/4 or node-positive esophageal cancer between 2004 and 2016 and who underwent chemoradiation and esophagectomy in the National Cancer Database were included. Multivariable regression was used to assess the association between socioeconomic variables and time to surgery (grouped into <56, 56-84, and 85-112 days). RESULTS: A total of 12 157 patients were included. Five-year overall survival was 39%, 35%, and 35% for the three groups examined. Postoperative 30- and 90-day mortality was increased in both the 56-84 days to surgery group (odds ratio [OR]: 1.30 and 1.20, respectively) and the 85-112 days group (OR: 1.37 and 1.56, respectively) when compared to <56 days. Patients of a minority race, public insurance, or lower income were more likely to have a longer time to surgery. CONCLUSION: Longer time to surgery is associated with increased postoperative mortality and is more common in patients with lower socioeconomic status. Further research exploring reasons for delays to esophagectomy among disadvantaged patients could help target interventions to reduce disparities.

Specimen oriented intraoperative margin assessment in oral cavity and oropharyngeal squamous cell carcinoma.

OBJECTIVE: Evaluate the oncologic outcomes and cost analysis of transitioning to a specimen oriented intraoperative margin assessment protocol from a tumour bed sampling protocol in oral cavity (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective case series and subsequent prospective cohort study SETTING: Tertiary care academic teaching hospital SUBJECTS AND METHODS: Retrospective case series of all institutional T1-T2 OCSCC or OPSCC treated with primary surgery between January 1st 2009 - December 31st 2014. Kaplan-Meier survival estimates with log rank tests were used to compare patients based on final margin status. Cost analysis was performed for escalation of therapy due to positive final margins. Following introduction of a specimen derived margin protocol, successive prospective cohort study of T1-T4 OCSCC or OPSCC treated with primary surgery from January 1st 2017 - December 31st 2018. Analysis and comparison of both protocols included review of intraoperative margins, final pathology and treatment cost. RESULTS: Analysis of our intra-operative tumour bed frozen section protocol revealed 15 of 116 (12.9%) patients had positive final pathology margins, resulting in post-operative escalation of therapy for 14/15 patients in the form of re-resection (7/14), radiation therapy (6/14) and chemoradiotherapy (1/14). One other patient with positive final margins received escalated therapy for additional negative prognostic factors. Recurrence free survival at 3 years was 88.4 and 50.7% for negative and positive final margins respectively (p = 0.048). Implementation of a specimen oriented frozen section protocol resulted in 1 of 111 patients (0.9%) having positive final pathology margins, a statistically significant decrease (p < 0.001). Utilizing our specimen oriented protocol, there was an absolute risk reduction for having a final positive margin of 12.0% and relative risk reduction of 93.0%. Estimated cost avoidance applying the specimen oriented protocol to our previous cohort was $412,052.812017 CAD. CONCLUSION: Implementation of a specimen oriented intraoperative margin protocol provides a statistically significant decrease in final positive margins. This change in protocol leads to decreased patient morbidity by avoiding therapy escalation attributable only to positive margins, and avoids the economic costs of these treatments.

Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis.

The role and prognostic value of tetraspanins (TSPANs) in vulvar squamous cell carcinoma (VSCC) remain poorly understood. We sought to primarily determine, at both the molecular and tissue level, the expression profile of the TSPANs CD9, CD63, CD81, and CD82 in archived VSCC samples (n = 117) and further investigate their clinical relevance as prognostic markers. Our studies led us to identify CD63 as the most highly expressed TSPAN, at the gene and protein levels. Multicomparison studies also revealed that the expression of CD9 was associated with tumor size, whereas CD63 upregulation was associated with histological diagnosis and vascular invasion. Moreover, low expression of CD81 and CD82 was associated with worse prognosis. To determine the role of TSPANs in VSCC at the cellular level, we assessed the mRNA levels of CD63 and CD82 in established metastatic (SW962) and non-metastatic (SW954) VSCC human cell lines. CD82 was found to be downregulated in SW962 cells, thus supporting its metastasis suppressor role. However, CD63 was significantly upregulated in both cell lines. Silencing of CD63 by siRNA led to a significant decrease in proliferation of both SW954 and SW962. Furthermore, in SW962 particularly, CD63-siRNA also remarkably inhibited cell migration. Altogether, our data suggest that the differential expression of TSPANs represents an important feature for prognosis of VSCC patients and indicates that CD63 and CD82 are likely potential therapeutic targets in VSCC.

Global, regional and national incidence, mortality and disability-adjusted life-years of skin cancers and trend analysis from 1990 to 2019: An analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Information about global and local epidemiology and trends of skin cancers is limited, which increases the difficulty of cutaneous cancer control. METHODS: To estimate the global spatial patterns and temporal trends of skin cancer burden. Based on the GBD 2019, we collected and analyzed numbers and age-standardized rates (ASR) of skin cancer incidence, disability-adjusted life years (DALYs) and mortality (ASIR, ASDR, and ASMR) in 204 countries from 1990 through 2019 were estimated by age, sex, subtype (malignant skin melanoma [MSM], squamous-cell carcinoma [SCC], and basal-cell carcinoma [BCC]), Socio-demographic Index (SDI), region, and country. Temporal trends in ASR were also analyzed using estimated annual percentage change. RESULTS: Globally, in 2019, there were 4.0 million BCC, 2.4 million SCC, and 0.3 million MSM. There were approximately 62.8 thousand deaths and 1.7 million DALYs due to MSM, and 56.1 thousand deaths and 1.2 million DALYs were attributed to SCC, respectively. The men had higher ASR of skin cancer burden than women. The age-specific rates of global skin cancer burden were higher in the older adults, increasing trends observed from 55 years old. Geographically, the numbers and ASR of skin cancers varied greatly across countries, with the largest burden of ASIR in high SDI regions. However, an unexpected increase was observed in some regions from 1990 to 2019, such as East Asia, and Sub-Saharan Africa. Although there was a slight decrease of the ASMR and ASDR, the global ASIR of MSM dramatically increased, 1990-2019. Also, there was a remarkable increase in ASR of BCC and SCC burden. CONCLUSIONS: Skin cancer remains a major global public health threat. Reducing morbidity and mortality strategies such as primary and secondary prevention should be reconsidered, especially in the most prevalent and unexpected increased regions, especially for those areas with the greatest proportions of their population over age 55.

Assessment of safety margin after microwave ablation of stage I NSCLC with three-dimensional reconstruction technique using CT imaging.

OBJECTIVE: To assess the ablative margin of microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) using a three-dimensional (3D) reconstruction technique. MATERIALS AND METHODS: We retrospectively analyzed 36 patients with stage I NSCLC lesions undergoing MWA and analyzed the relationship between minimal ablative margin and the local tumor progression (LTP) interval, the distant metastasis interval and disease-free survival (DFS). The minimal ablative margin was measured using the fusion of 3D computed tomography reconstruction technique. RESULTS: Univariate and multivariate analyses indicated that tumor size (hazard ratio [HR] = 1.91, P < 0.01; HR = 2.41, P = 0.01) and minimal ablative margin (HR = 0.13, P < 0.01; HR = 0.11, P < 0.01) were independent prognostic factors for the LTP interval. Tumor size (HR = 1.96, P < 0.01; HR = 2.35, P < 0.01) and minimal ablative margin (HR = 0.17, P < 0.01; HR = 0.13, P < 0.01) were independent prognostic factors for DFS by univariate and multivariate analyses. In the group with a minimal ablative margin < 5 mm, the 1-year and 2-year local progression-free rates were 35.7% and 15.9%, respectively. The 1-year and 2-year distant metastasis-free rates were 75.6% and 75.6%, respectively; the 1-year and 2-year disease-free survival rates were 16.7% and 11.1%, respectively. In the group with a minimal ablative margin ≥ 5 mm, the 1-year and 2-year local progression-free rates were 88.9% and 69.4%, respectively. The 1-year and 2-year distant metastasis-free rates were 94.4% and 86.6%, respectively; the 1-year and 2-year disease-free survival rates were 88.9% and 63.7%, respectively. The feasibility of 3D quantitative analysis of the ablative margins after MWA for NSCLC has been validated. CONCLUSIONS: The minimal ablative margin is an independent factor of NSCLC relapse after MWA, and the fusion of 3D reconstruction technique can feasibly assess the minimal ablative margin.

Socioeconomic Factors Affect Presentation Stage and Survival in Sinonasal Squamous Cell Carcinoma.

OBJECTIVES: Socioeconomic factors affect oncologic outcome in sinonasal squamous cell carcinoma (SNSCC). However, the relationship between these factors and stage at presentation (SAP)-a critical, early point in the care cycle-is not known. This study sought to determine the role of race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors in SAP and survival among patients with advanced SNSCC. STUDY DESIGN: Retrospective cohort study. METHODS: Using the National Cancer Database, 6,155 patients with SNSCC were identified and divided into those with "early" (Stage I or II; 2,212 (35.9%)) versus "advanced" (Stage III or IV; 3,943 (64.1%)) disease. Associations between sociodemographic and socioeconomic factors on SAP and survival were analyzed using multivariable logistic regression and Cox proportional hazard models. RESULTS: Black (odds ratio [OR]: 2.18, CI: 1.74-2.76), Asian and Pacific Islander (API) (OR: 2.37, CI: 1.43-4.14), and Medicaid or uninsured (OR: 2.04, CI: 1.66-2.53) patients were more likely to present with advanced disease. Among patients with advanced disease, API patients demonstrated the highest 10-year survival rate (30.2%), and Black patients had the lowest 2-, 5-, and 10-year survival rates (47.7%, 31.9% and 19.2%, respectively). Older age (HR:1.03, CI:1.03-1.04), Black race (HR:1.39, CI:1.21-1.59), Medicaid or uninsured status (HR:1.48, CI:1.27-1.71), and treatment at a community hospital (HR:1.25, CI:1.14-1.37) were associated with poorer overall survival among patients with advanced disease. CONCLUSIONS: Factors including race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors influence SAP and survival in SNSCC. An improved understanding of how these factors relate to outcomes may elucidate opportunities to address gaps in education and access to care in vulnerable populations. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2421-2428, 2021.

Disease Profile and Oncologic Outcomes After Delayed Diagnosis of Human Papillomavirus-Associated Oropharyngeal Cancer.

OBJECTIVE: Diagnostic delay in human papillomavirus-associated oropharynx squamous cell carcinoma (HPV(+)OPSCC) is common due to nonspecific symptoms. We aim to describe the disease burden and oncologic outcomes of patients with HPV(+)OPSCC diagnosed >12 months after symptom onset. STUDY DESIGN: This is a retrospective cohort study of HPV(+)OPSCC patients receiving intent-to-cure treatment (including surgery ± adjuvant therapy or primary chemoradiation). SETTING: 2006-2016, tertiary care center. METHODS: Tumor stage was compared between patients with and without delayed diagnosis using χ2 tests. Kaplan-Meier survival analysis with univariate and multivariable Cox regressions were used to determine the effect of diagnostic delay on oncologic outcomes. RESULTS: In total, 664 patients were included. Compared to patients diagnosed <12 months from symptom onset (n = 601), those diagnosed at >12 months (n = 63) were more likely to have T4 disease and higher overall American Joint Committee on Cancer (AJCC) clinical stage at presentation (P < .01 for both). At 5 years, rates of overall survival, cancer-specific survival, progression-free survival, and distant metastases-free survival in the delayed diagnosis cohort were 80%, 90%, 80%, and 89%, respectively. A >12-month delay in diagnosis did not significantly impact overall survival (adjusted hazard ratio [aHR], 1.16; 95% CI, 0.58-2.31), cancer-specific survival (aHR, 0.83; 95% CI, 0.29-2.39), progression-free survival (aHR, 1.15; 95% CI, 0.56-2.37), or distant metastases-free survival (aHR, 1.00; 95% CI, 0.42-2.40) after adjusting for age, sex, and clinical AJCC stage (P > .05 for all). CONCLUSIONS: Delayed diagnosis of HPV(+)OPSCC is associated with greater burden of disease at presentation, but oncologic outcomes remain favorable across treatment modalities. When appropriate, intent-to-cure therapy should be pursued despite diagnostic delay. LEVEL OF EVIDENCE: Level III.

Anal cancer survival: a socioeconomic analysis.

INTRODUCTION: Squamous cell carcinoma is the most common variant of anal malignancy. Certain disease-related factors have been established in determining survival. These include tumour size, differentiation and nodal involvement. Other factors such as HIV status, human papillomavirus infection, smoking and socioeconomic disparity may have important roles, however few data are available on the UK population. We aim to correlate social deprivation and survival of anal cancer patients at a tertiary centre. MATERIALS AND METHODS: All consecutive cases diagnosed with anal squamous cell carcinoma and treated as per local protocol between July 2010 and April 2017 were included. The pathological and demographical details were collected from a prospectively maintained database. Socioeconomic deprivation was defined for each postcode using the Index of Multiple Deprivation decile compiled by local governments in England. Survival was estimated using Kaplan-Meier analysis and Cox regression was used to investigate the effect of different factors on overall survival. RESULTS: A total of 129 patients with anal squamous cell carcinoma over a median follow-up of 43 months were included. Overall survival for the entire patient cohort was 87.7% (95% confidence interval, CI, 82.0-93.7%), 75.5% (95% CI 67.5-84.5%) and 68.9% (95% CI 59.7-79.6%) at one year, three years and five years, respectively. On multivariate analysis, Index of Multiple Deprivation and income do not significantly influence overall survival (p = 0.79, hazard ratio, HR, 1.07; 95% CI 0.61-1.63), (p = 0.99, HR=1.00; 95% CI 0.61-1.63), respectively. Increased risk of death was observed for male sex (p = 0.02, HR=2.80; 95% CI 1.02-5.50) and larger tumour size (p = 0.01, HR=1.64; 95% CI 1.12-2.41). CONCLUSION: In contrast to US studies, there is little difference in survival between the least deprived and most deprived groups. We attribute this to equal access to intensity-modulated radiation therapy-based chemoradiotherapy. Thus, a highly effective treatment made available to all mitigates any survival difference between socioeconomic groups.

Does insurance type influence overall survival in patients with laryngeal squamous cell carcinoma?

OBJECTIVE: Patients with head and neck cancer with Medicaid or no insurance present at a more advanced stage and have lower survival. This study is one of the first to examine the relationship between specific insurance types and overall survival for laryngeal squamous cell carcinoma patients. STUDY DESIGN: Retrospective chart review. SETTING: Henry Ford Cancer Institute. SUBJECTS AND METHODS: A retrospective database review was performed using the Henry Ford Virtual Data Warehouse Tumor Registry. Six hundred and fifty patients diagnosed with laryngeal squamous cell carcinoma were identified. Insurance groups analyzed were fee for service, health maintenance organization, Henry Ford Medical Group - a managed care type insurance, Medicare and Medicaid/uninsured. Cox proportional hazards and Kaplan-Meier curves were generated to analyze overall survival and display survival differences respectively. RESULTS: The uninsured group had the lowest median survival time of 29.8 months (95% CI: 20.3-44.8) and the highest HR of 1.85 (95% CI 1.16-2.93) as compared to the HMO group at p < 0.001. Patients with fee for service insurance had longer overall survival compared to the other insurance types. Patients with fee for service insurance also had a high proportion of patients with advanced stage disease, but a younger mean age. Henry Ford Medical Group had a higher mean age and no statistically significant difference in survival when compared to fee for service. (p = 0.999) After controlling for socioeconomic status, insurance type remains a significant predictor of overall survival. CONCLUSIONS: Fee for service had the highest overall survival of the different insurance types, but it was only statistically significant when compared to the Medicaid/uninsured group.

The role of electrochemotherapy with intratumoral bleomycin for early tongue carcinoma.

BACKGROUND: The role of electrochemotherapy (ECT) using intratumoral bleomycin and electroporation as a first line treatment for oral tongue carcinoma has not been defined. AIMS/OBJECTIVES: To evaluate the method of ECT in oral tongue carcinoma. MATERIAL AND METHODS: Twenty-one successive patients with primary T1-T2 oral cancer predominantly of the oral tongue underwent either ECT (test; n = 9), or standard surgical resection and reconstruction (control; n = 12). Outcome variables were: local recurrence rates, 10-year-survival, adverse events, treatment cost, and quality of life. RESULTS: The 10-year local recurrence rate (44.4%) was higher and the tumour-specific survival rate (55.6%) was lower in the ECT group compared to the control group (17% and 91.6%, respectively). Postoperative haemorrhage, dysphagia, and pain were more frequent in ECT patients, treatment time was shorter, but treatment cost was higher. Quality of life was not improved by ECT. CONCLUSIONS AND SIGNIFICANCE: Our results indicate that ECT seems not as suitable for the treatment of early tongue cancer as it is for neoplastic and metastatic skin lesions and less favourable than standard surgical therapy.

Palliative radiotherapy after oesophageal cancer stenting (ROCS): a multicentre, open-label, phase 3 randomised controlled trial.

BACKGROUND: Patients with advanced oesophageal cancer have a median survival of 3-6 months, and most require intervention for dysphagia. Self-expanding metal stent (SEMS) insertion is the most typical form of palliation in these patients, but dysphagia deterioration and re-intervention are common. This study examined the efficacy of adjuvant external beam radiotherapy (EBRT) compared with usual care alone in preventing dysphagia deterioration and reducing service use after SEMS insertion. METHODS: This was a multicentre, open-label, phase 3 randomised controlled trial based at cancer centres and acute care hospitals in England, Scotland, and Wales. Patients (aged ≥16 years) with incurable oesophageal carcinoma receiving stent insertion for primary management of dysphagia were randomly assigned (1:1) to receive usual care alone or EBRT (20 Gy in five fractions or 30 Gy in ten fractions) plus usual care after stent insertion. Usual care was implemented according to need as identified by the local multidisciplinary team (MDT). Randomisation was via the method of minimisation stratified by treating centre, stage at diagnosis (I-III vs IV), histology (squamous or non-squamous), and MDT intent to give chemotherapy (yes vs no). The primary outcome was difference in proportions of participants with dysphagia deterioration (>11 point decrease on patient-reported European Organisation for Research and Treatment of Cancer quality of life questionnaire-oesophagogastric module [QLQ-OG25], or a dysphagia-related event consistent with such a deterioration) or death by 12 weeks in a modified intention-to-treat (ITT) population, which excluded patients who did not have a stent inserted and those without a baseline QLQ-OG25 assessment. Secondary outcomes included survival, quality of life (QoL), morbidities (including time to first bleeding event or hospital admission for bleeding event and first dysphagia-related stent complications or re-intervention), and cost-effectiveness. Safety analysis was undertaken in the modified ITT population. The study is registered with the International Standard Randomised Controlled Trial registry, ISRCTN12376468, and ClinicalTrials.gov, NCT01915693, and is completed. FINDINGS: 220 patients were randomly assigned between Dec 16, 2013, and Aug 24, 2018, from 23 UK centres. The modified ITT population (n=199) comprised 102 patients in the usual care group and 97 patients in the EBRT group. Radiotherapy did not reduce dysphagia deterioration, which was reported in 36 (49%) of 74 patients receiving usual care versus 34 (45%) of 75 receiving EBRT (adjusted odds ratio 0·82 [95% CI 0·40-1·68], p=0·59) in those with complete data for the primary endpoint. No significant difference was observed in overall survival: median overall survival was 19·7 weeks (95% CI 14·4-27·7) with usual care and 18·9 weeks (14·7-25·6) with EBRT (adjusted hazard ratio 1·06 [95% CI 0·78-1·45], p=0·70; n=199). Median time to first bleeding event or hospital admission for a bleeding event was 49·0 weeks (95% CI 33·3-not reached) with usual care versus 65·9 weeks (52·7-not reached) with EBRT (adjusted subhazard ratio 0·52 [95% CI 0·28-0·97], p=0·038; n=199). No time versus treatment interaction was observed for prespecified QoL outcomes. We found no evidence of differences between trial group in time to first stent complication or re-intervention event. The most common (grade 3-4) adverse event was fatigue, reported in 19 (19%) of 102 patients receiving usual care alone and 22 (23%) of 97 receiving EBRT. On cost-utility analysis, EBRT was more expensive and less efficacious than usual care. INTERPRETATION: Patients with advanced oesophageal cancer having SEMS insertion for the primary management of their dysphagia did not gain additional benefit from concurrent palliative radiotherapy and it should not be routinely offered. For a minority of patients clinically considered to be at high risk of tumour bleeding, concurrent palliative radiotherapy might reduce bleeding risk and the need for associated interventions. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Days alive and out of hospital after treatment for oropharyngeal squamous cell carcinoma with primary transoral robotic surgery or radiotherapy - a prospective cohort study.

BACKGROUND: With the rising incidence of oropharyngeal squamous cell cancer, there is a need to assess the burden of treatment. AIMS/OBJECTIVES: This study assessed 'days alive and out of hospital' (DAOH) in a cohort of patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with either transoral robotic surgery (TORS) or radiotherapy (RT). MATERIAL AND METHODS: A prospective cohort study conducted between May 2017-June 2019. Primary outcome was DAOH in the first 30 days after treatment (DAOH30). The secondary outcome was DAOH180. RESULTS: Forty-four patients were included, 31 treated with TORS and 13 with RT. Patients treated with TORS had a median DAOH30 of 25 (IQR 22.8-26) including a required four-day postoperative stay- and a median DAOH180 of 168 (IQR 163-171.3). In contrast, patients treated with RT had a median DAOH30 of 30 (IQR 26-30) and a DAOH180 of 143 days (IQR 135.5-149). CONCLUSIONS AND SIGNIFICANCE: DAOH has not been examined in oropharyngeal cancer before. We found, patients overall spent 92.5% of the first 180 days alive and out of hospital. Patients treated with TORS had high DAOH30, which remained high in DAOH180, while patients treated with RT with reduced DAOH30, had reduced DAOH180 calling for further large-scale studies.

Disparities in Mortality from Larynx Cancer: Implications for Reducing Racial Differences.

OBJECTIVE: Race predicts overall mortality (OM) of laryngeal squamous cell carcinoma (LSCC) in the United States (US). We assessed whether racial disparities affect cancer-specific mortality (CSM) using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Adults with LSCC from 2004 to 2015 were selected. Univariable and multivariable Cox proportional hazards and Fine-Gray competing-risks regression analysis adjusted for clinicodemographic factors defined hazard ratios (aHR). RESULTS: We identified 14,506 patients. The median age was 63 years. Most were male (11,725, 80.8%) and white (11,653, 80.3%), followed by Black (2294, 15.8%). Most had early-stage disease (7544, 52.0%) and received radiotherapy only (4107, 28.3%), followed by chemoradiation (3748, 25.8%). With median follow-up of 60 months, overall 3- and 5-year OM were 34.0% and 43.2%; CSM were 16.0% and 18.9%, respectively. Black patients had higher OM than white patients on univariable (HR 1.35, 95% CI, 1.26-1.44, P < .001) and multivariable (aHR 1.10, 95% CI, 1.02-1.18, P = .011) analyses. Black patients had higher CSM on univariable analysis (HR 1.22, 95% CI, 1.09-1.35, P < .001) but not on multivariable CSM analysis (aHR 1.01, 95% CI, 0.90-1.13, P = .864). On multivariable analysis, year of diagnosis, age, disease site, stage, treatment, nodal metastasis, marital status, education, and geography significantly predicted CSM. CONCLUSION: On multivariable analyses controlling for sociodemographic, clinical, and treatment characteristics, Black and white patients differed in OM but not in CSM. However, Black patients presented with greater proportions of higher stage cancers and sociodemographic factors such as income and marital status that were associated with worse outcomes. Efforts to target sociodemographic disparities may contribute to the mitigation of racial disparities in LSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1147-E1155, 2021.

Insurance Status as a Predictor of Treatment in Human Papillomavirus Positive Oropharyngeal Cancer.

OBJECTIVES: The link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) is well known. Locally advanced, HPV-positive OPC (HPV OPC) can be treated with either chemoradiation or primary surgery with or without adjuvant therapy. Head and neck cancer patients with government insurance or uninsured have been shown to have worse prognosis than similar patients with private insurance. In this study, we aimed to determine if insurance status would predict treatment modality in patients with HPV OPC. STUDY DESIGN: A retrospective analysis using the National Cancer Database (NCDB). METHODS: The National Cancer Database was used to identify patients with HPV OPC who underwent primary surgery or primary chemoradiation from 2010-2015. Insurance status was categorized as government, private, or no insurance. The relationship between insurance status and treatment was investigated using Chi square and multivariate regression models. Kaplan-Meier analyses were performed comparing overall survival (OS) by insurance status. RESULTS: There were 10,606 patients were included. There was a statistically significant correlation between insurance status and primary treatment modality for HPV OPC (P < .001). Patients with government insurance were 19.3% less likely to undergo surgery and uninsured patients were 36.9% less likely to undergo primary surgery when compared to those with private insurance (P < .001), even after correcting for TNM stage in multivariate analysis. There was an improved 5-year OS for patients with private insurance (86.6%) versus both government insurance (68.4%) and no insurance (69.9%) (P < .001). CONCLUSIONS: Patients with private insurance are more likely to undergo primary surgery in HPV OPC and have improved overall survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:776-781, 2021.

Improved Tumor Control Related to Radiotherapy Technological Development for Hypopharyngeal Cancer.

OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma of the hypopharynx (SCCHP) is associated with worse survival compared to other head and neck subsites. This report quantifies the impact of technological improvements in radiotherapy (RT) on outcomes over 6 decades. METHODS: Patients with SCCHP receiving curative-intent treatment between 1962 and 2015 were retrospectively reviewed. Kaplan-Meier analyses of freedom from local recurrence (FFLR), progression-free survival (PFS), and overall survival (OS) were compared across treatment eras and radiation techniques. Multivariable Cox proportional hazards modeling was performed to specify the effect of RT technique. RESULTS: One hundred thirty-four patients had a median follow-up of 17 months (IQR = 9-38). There were no differences in staging or use of surgery over time, but use of chemotherapy concurrent with RT increased (P < .001) beginning in the 2000s. The 24-month FFLR using two-dimensional RT (2D-RT), three-dimensional conformal RT (3D-CRT), and intensity-modulated RT (IMRT) was 52%, 55%, and 80%, respectively; 24-month PFS was 39%, 46%, and 73%, respectively; and 24-month OS was 27%, 40%, and 68%, respectively. OS (P = .01), PFS (P = .03), and FFLR (P = 0.02) were improved with IMRT over 2D-RT, and FFLR appeared to be improved over 3D-CRT (P = .06). Controlling for chemotherapy use and other major variables, IMRT produced a strong influence over FFLR (adjusted hazard ratio [HR] = 0.2, 95% confidence interval [CI]: 0.0-1.2, P = .08) and a benefit in OS (adjusted HR = 0.1, 95% CI: 0.0-0.4, P = .005). CONCLUSIONS: Across 6 decades, patient and tumor characteristics remained similar whereas use of chemoradiation increased and IMRT was adopted. The introduction of IMRT was associated with improved FFLR, PFS, and OS, and a reduction in acute toxicity as compared to earlier radiation technologies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E452-E458, 2021.

Socioeconomic and Racial Disparities and Survival of Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status (SES) using the National Cancer Database (NCDB). STUDY DESIGN: Population-based cohort study. SETTING: Racial and socioeconomic disparities in survival of OPSCC have been previously acknowledged. However, the distribution of HPV-related cancers and its influence on survival in conjunction with race and SES remain unclear. SUBJECTS AND METHODS: All patients with OPSCC in the NCDB with known HPV status from 2010 to 2016 were included. Differences in presentation, HPV status, treatment, and outcomes were compared along racial and socioeconomic lines. Univariable and multivariable Cox regression survival analyses were performed. RESULTS: In total, 45,940 patients met criteria. Most were male (38,038, 82.8%), older than 60 years (23,456, 51.5%), and white (40,156, 87.4%), and lived in higher median income areas (>$48,000, 28,587, 62.2%). Two-thirds were HPV positive (31,007, 67.5%). HPV-negative disease was significantly more common in lower SES (<$38,000, 2937, 41.5%, P < .001) and among blacks (1784, 55.3%, P < .001). Median follow-up was 33 months. Five-year overall survival was 81.3% (95% CI, 80.5%-82.1%) and 59.6% (95% CI, 58.2%-61.0%) in HPV-positive and HPV-negative groups, respectively. In univariable and multivariable analyses controlling for HPV status, age, stage, and treatment, black race (hazard ratio [HR], 1.22; 95% CI, 1.11-1.34; P < .001) and low SES (HR, 1.58; 95% CI, 1.45-1.72; P < .001) were associated with worse survival. CONCLUSION: Significant differences in HPV status exist between socioeconomic and racial groups, with HPV-negative disease more common among blacks and lower SES. When controlling for HPV status, race and SES still influence outcomes in oropharyngeal cancers.

The effect of centralization of care on overall survival in primary urethral cancer.

PURPOSE: Centralization of care to high-volume centers improves outcomes across urologic malignancies, but there exists a paucity of data for low-incidence cancers. Given the rarity of primary urethral cancer (UC) and the need for complex multidisciplinary treatment, we sought to evaluate differences in practice patterns and clinical outcomes across types of treating facilities. MATERIALS AND METHODS: We identified all patients diagnosed with UC from 2004 to 2016 in the National Cancer Database. The Kaplan-Meier method was used to evaluate overall survival (OS) and multivariable Cox regression analysis was used to investigate independent predictors of OS. The chi-square test was used to analyze differences in practice patterns. RESULTS: We identified 6,445 patients with UC. Median overall survival was 40.5 months (interquartile range 38.4-42.6). There was a significant difference in OS based upon facility type, and this difference remained significant on subgroup analysis for squamous cell carcinoma and urothelial carcinoma. Academic centers had superior OS on pairwise comparisons (all P< 0.05) and were associated with decreased risk of death, hazard ratio 0.858 (95% confidence interval 0.749-0.983). Academic centers had a significantly greater frequency of neoadjuvant/adjuvant chemotherapy and radiation (P < 0.001). Academic centers performed radical surgery in 34.1% of patients compared to 14.5% in community programs (P < 0.001), and regional lymphadenectomy in 31.6% of patients compared to 13.2% in community programs (P < 0.001). CONCLUSION: There exist significant differences in survival for patients with UC based upon treating facility. Variations in practice patterns including multimodal treatment, radical surgery, and regional lymphadenectomy may contribute to the observed differences in clinical outcomes.